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Life course perspectiveson coronary heart disease,
stroke and diabetes
WHO/NMH/NPH/01.4ORIGINAL: ENGLISH
DISTR.: GENERAL
Ageing and Life CourseDepartment of Noncommunicable Diseases Prevention and Health Promotion
Noncommunicable Diseases and Mental Health Cluster
WORLD HEALTH ORGANIZATION
Key issues and implicationsfor policy and research
SUMMARY REPORTOF A MEETING OF EXPERTS
24 MAY 2001
ACCUMULATEDNCDRISK
AGE
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31 2 4
The risk of noncommunicable diseases accumulates with age and is influenced byfactors acting at all stages of the life span. The main factors at different stages of life
include the following:
1 Fetal Life
fetal growth, maternal nutritional status, socioeconomic position at birth
2 Infancy and Childhood
growth rate, breastfeeding infectious diseases, unhealthy diet, lack of physicalactivity, obesity socioeconomic position
3 Adolescence
unhealthy diet, lack of physical activity, obesity tobacco and alcohol use
4 Adult life
know adult behavioural and biological risk factors
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Life course perspectiveson coronary heart disease,
stroke and diabetesKey issues and implications
for policy and research
SUMMARY REPORT
OF A MEETING OF EXPERTS
24 MAY 2001
WHO/NMH/NPH/01.4 ORIGINAL: ENGLISH DISTR.: GENERAL
Ageing and Life CourseDepartment of Noncommunicable Diseases Prevention and Health Promotion
Noncommunicable Diseases and Mental Health Cluster
WORLD HEALTH ORGANIZATIONGeneva
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Acknowledgements
The World Health Organization wishes to acknowledge the support from the Govern-
ment of Japan for the organization of the first meeting of experts on life course and
health and the finalization of this report.
Copies can be obtained from:
Ageing and Life Course
Dept. of Noncommunicable Diseases Prevention and Health Promotion
Noncommunicable Diseases and Mental Health Cluster
NMH/NPH/ALC
20 Avenue Appia
1121 Geneva 27
Switzerland
Fax: +41 (22) 7914839
e-mail: [email protected]
Suggested Citation:
Aboderin, I., Kalache, A., Ben-Shlomo, Y., Lynch, J.W., Yajnik, C.S., Kuh, D., Yach, D.
(2001)Life Course Perspectives on Coronary Heart Disease, Stroke and Diabetes: Key Issues
and Implications for Policy and Research. Geneva, World Health Organization
World Health Organization 2001
This document is not a formal publication of the World HealthOrganization (WHO), and all rights are reserved by the Organization.The document may, however, be freely reviewed, abstracted,reproduced or translated, in part or in whole, but not for sale nor foruse in conjunction with commercial purposes.
The views expressed in documents by named authors are solely theresponsibility of those authors.
Designed by minimum graphicsPrinted in Switzerland
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Contents
iii
Executive Summary 1
Introduction: Setting the scene 2
Part I The life course perspective and NCD prevention:
potential and challenge 5
1.1 Introduction 71.2 Global trends in CVD and diabetes 7
1.3 The life course perspectivepotential
and challenge 8
Part II Key themes and gaps in evidence on life course
links to disease 11
2.1 Introduction 13
2.2 Key themes and gaps in evidence on life course
links to disease 14
Part III Emerging policy implications and research priorities 23
3.1 Emerging implications and recommendations
for policy 25
3.2 Key priority areas for future research 28
3.3 Conclusion: Taking policy and research
agendas forward 30
Bibliography 31
Appendix A. List of participants 34
Appendix B. Programme of Meeting 35
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1
Executive Summary
The Life Course and Health Perspec-tive considers chronic disease interms of the social and physical hazards,
and the consequent biological, behav-
ioural and psychosocial processes, that
operate across all stages of the life span
to cause or modify risk of disease.This perspective carries a substantial
potential for identifying the most appro-
priate and effective policies for NCD
prevention and health promotiona po-
tential that is yet to be fully realized in
public health policy.
Through the preparation for, and the
conduct of a meeting of experts on life
course and health (24 May, 2001), the
WHO Department of NoncommunicableDiseases Prevention and Health Promo-
tion (NPH) made a first step towards har-
nessing the potential of the life course
approach for policy.
The meeting has established the state
of the art knowledge regarding life course
impacts on risk of coronary heart disease,
stroke and diabetes and, on the basis of
this, has identified emerging agendas for
policy and research. The limited initial
focus on three diseases was deemed nec-
essary for the task to remain manageable.
However, it provides a starting point upon
which future assessments of life course
and other NCDs can build.
The emerging policy recommenda-
tions follow a hierarchy according to
the firmness of available evidence. The
strongest recommendation, currently, is
to continue the focus on the major known
risk factors. In doing so, particular atten-
tion should be paid to primordial/primary
prevention strategies to counter the emer-
gence of risk factors and behaviours in
childhood or adolescence, particularly in
developing countries. Most importantly,
such strategies must take into account thevaried processes by which urbanisation
and westernisation can lead to risk be-
haviours and factors in different socio-
economic contexts and populations. It is
important to recognize the cultural, eco-
nomic and social circumstances within
which such behaviours and risks emerge,
and that these may be specific to differ-
ent countries in different stages of eco-
nomic development. Thus, research toinform the development of such preven-
tive strategies in individual countries is
urgently needed.
Despite the high profile of evidence
linking early life factors such as reduced
fetal growth to later disease, evidence is
still insufficient for firm policy recom-
mendations to be made. Further research
is urgently needed to establish the rela-
tive role and importance of early life ex-
posures, and the mechanisms by which
they affect future risk of disease. Key prior-
ity areas for research have been identified.
NPH is taking forward the policy and
research agendas emerging in light of
current evidence on life course, through
collaborative work and consultation
across departments within WHO, and
with outside institutions.
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2
LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
Introduction
v. To establish a WHO expert advisory
group on life course and health
In order to achieve these objectives,
twenty-one experts/researchers repre-
senting both developed and developing
countries (see Appendix A), were brought
together in three days of structured dis-
cussions. The basic framework for the
discussions were the central concepts and
perspectives of a life course approach to
chronic disease, as set out in a background
paper prepared, in consultation with ALC,
by the two main scientific advisers to the
meeting: Dr. Ben-Shlomo, University of
Bristol; and Dr. Kuh, University College
London (see Appendix B).
The structure of the discussions wasdevised, in close consultation with Drs.
Kuh and Ben-Shlomo, on the basis of the
main themes and issues identified by the
expert invitees in answer to a set of ques-
tions regarding life course research and
its implications prior to the meeting. A
synthesis of the experts comments, cir-
culated to all experts in advance, provided
a main background for the discussions.
A second background paper provideda broad overview of life course research
and emerging evidence in the develop-
ing world. The paper was prepared in
view of the fact that, to date, no compre-
hensive reviews on life course research
in developing countries exist. This con-
trasts with the growing prominence that
life course research has been attaining in
the developed world, reflected in the
number of recent reviews (e.g Kuh and
Ben-Shlomo, 1997; Kuh and Hardy, forth-
Setting the scene:
Purpose of the meeting
In May 2001, a first meeting of expertson Life Course and Health was con-vened by the WHO Ageing and Life
Course Programme (ALC) in the Depart-
ment of Noncommunicable Disease Pre-
vention and Health Promotion (NPH).
The main aim of the meeting was to es-
tablish the state of the art in knowledge
regarding life course influences on risk
of chronic disease (specifically coronary
heart disease, stroke and diabetes) and,
on the basis of that, to pinpoint key im-
plications for policy and research.
An important aspect of the meeting
was to specifically consider this scientificknowledge and its implications within
both developed and developing world
contexts.
The specific aims of the meeting were:
i. To establish what evidence cur-
rently exists regarding the role of
life course influences on risk of
coronary heart disease, stroke and
diabetes
ii. To identify emerging indications
for policy and to examine the fea-
sibility for action/intervention/
policy development
iii. To pinpoint gaps in knowledge,
which need to be addressed by im-
mediate research
iv. To stimulate policy makers to take
into account the life course per-
spective
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3
INTRODUCTION
coming; Terry and Susser, 2001), as well
as critical commentaries and discussions
(e.g Kramer, 2000; Lucas et al. 1999; the
Lancet, 2001)The meeting itself consisted of five
main sessions. The first four, each,
focused on one of the following key bio-
logical or lifestyle related domains:
Obesity and height in relation to
CVD and diabetes
Blood pressure in relation to CVD
Dyslipidaemias and glucose intoler-
ance in relation to CVD and diabe-
tes
Life course roots of unhealthy life-
styles (tobacco use, physical inactiv-
ity, unhealthy diet)
While there is considerable overlap
between these domains, the division was
deemed necessary for rendering discus-
sions in the sessions manageable. The
discussions of each domain focused onthe following aspects:
Secular trends for developed and
developing countries
Patterns with respect to gender,
ethnicity, adult socio-economic
status
Life course determinants in adult-
hood, childhood, in utero, and
intergenerationally
Interactions with earlier life risk
factors
Needs for further research
A fifth session discussed the potential
underlying mechanisms linking life
course exposures to CVD and diabetes.
Specific points considered included:
Genetics
Intergenerational factors (genetics;
imprinting; maternal vitality; shared
socio-economic status)
Intrauterine factors; nutrition inpregnancy, fetal nutrition
Post-natal factors; infectious disease,
childhood diet, psychosocial influ-
ences, timing and duration of
puberty
Endocrine programming and modu-
lation
The five main sessions were followed
by several small-group and plenary dis-cussions which were dedicated to teasing
out emerging implications for policy and
research and then developing these into
firm policy and research agendas. In par-
ticular experts were asked to consider:
Evidence for reversibility and effec-
tive interventions
Need to modify current health poli-
cies (population and/or high risk)
Evidence for simple policy interven-
tions that influence pathways
This abridged report of the meeting
provides an overview of the identified key
themes and gaps in current understand-
ing of the life course influences on CHD,
stroke and diabetes; the emerging impli-
cations for public health policy, and the
priority areas for future research.
The detailed review of the state of theart evidence on life course is presented
in the full version of the meetings report.
Structure of the report
This report is divided into two parts:
Part I provides the background to, ration-
ale for, and nature of WHOs initiative on
the life course. It begins by showing how
the life-course perspective fits into, andis a vital underpinning of WHOs work on
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NCD prevention and health promotion,
and by briefly outlining the alarming glo-
bal NCD trends, especially in CVD and
diabetes, that make this work imperative.This is followed by a description of the
content, focus and basis of the life course
perspective, emphasizing its potential for
effective policy development. Finally, the
key challenges that need to be met in
order to translate this potential into prac-
tice are described.
Part II provides an overview of the main
conclusions emerging from the meetingsdiscussions. It describes the key themes,
issues, and the main gaps in current
knowledge regarding the influence of life
course factors on disease risk.
Part III pinpoints the emerging recom-
mendations for public health policy and,
finally, highlights the priority areas for
future research.
A comprehensive review of the current
evidence on life course and CHD, stroke
and diabetes is available in the full report:
Life Course Perspectives on Coronary Heart
Disease, Stroke and Diabetes: The Evidenceand Implications for Policy and Research.
4
LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
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PART I
Life course asa central part of WHOs work on
NCD prevention and healthpromotion
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1.1 Introduction
The WHO initiative on life course and
health is situated within, and is a cen-tral aspect of the work of the Department
of Noncommunicable Disease (NCD)
Prevention and Health Promotion (NPH).
The departments overall goal is to pre-
vent noncommunicable diseases and thus
to reduce premature morbidity, mortal-
ity and disability caused by them. Particu-
lar focus is given to most common NCDs
such as cardiovascular diseases (CVD)
and diabetes, as they cause much human
suffering, pose substantial threats to the
economies of individual countries, and
are important in the increasing health
inequalities between countries and within
populations worldwide.
1.2 Global trends in CVDand diabetes
Although already high, the burden of CVD
and diabetes is expected to rise furtherin the coming decadesabove all in de-
veloping countries, i.e.
those countries with the
least resources to effec-
tively deal with them (see
e.g. Murray and Lopez,
1996):
In developed coun-
tries, cardiovascular
diseases are andwill remain the first
cause of death and
disability, despite
the gradual decline
in disease rates experienced in most
of them in the last few decades. In
2000, 48.6% of deaths were caused
by CVD. By 2020, still 46.4% of all
deaths are expected to be attribut-
able to CVD. Meanwhile, thenumber of those suffering from dia-
betes will have risen from 51 mil-
lion in 1995 to 72 million in 2025.
In the developing world, CVD willsoon become the main cause of
death and disability: by 2020, a third
(33.8%) of all deaths are expected
to be due to CVD. The number of
those with diabetes will increase
more than 2.5 times, from 84 mil-
lion in 1995 to 228 million in 2025.
It is projected that by 2020 71% of
ischaemic heart disease (IHD)
deaths, 75% of stroke deaths and70% of diabetes deaths will occur in
developing countries
The current epidemic in adult and
childhood obesity, not just in devel-
oped but also in many developing
countries may indicate even sharper
rises in the burden of CVD and dia-
betes.
The spectre of rising CVD and diabe-
tes underscores the imperative need to
develop effective and
appropriate prevention
policies, especially in
poor and marginalized
populations. Such poli-
cies, as has long been
recognized, need to
address the major risk
factors predisposing to
disease (the currentfocus is on the behav-
ioural risk factors smok-
ing, physical inactivity
and unhealthy diet), and
take into consideration underlying eco-
nomic, social, gender, political, behav-
ioural and environmental factors that
foster disease risk.
However, what the most valuable con-
crete strategies are in different contextsand populations, whom they should be
PART I. LIFE COURSE AS A CENTRAL PART OF WHOS WORK ON NCD PREVENTION AND HEALTH PROMOTION
7
Although already
high, the burden of CVD
and diabetes is expected
to rise further in the
coming decadesabove
all in developing
countries, i.e. those
countries with the leastresources to effectively
deal with them.
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8
LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
targeted at, when and how, remains to be
firmly established and will depend in
large part on the cultural, social and eco-
nomic conditions.This represents the core charge of
NPHs work and is the reason why NPH
has adopted the life
course as the underpin-
ning perspective of its
work. In doing so, WHO
recognizes the potential
of the life course perspec-
tive to enable policy-mak-
ers to identify the mosteffective and appropriate
prevention strategies and
to gain maximum lever-
age for interventions
where prevention re-
sources may be scarce.
1.3 The life course perspectivepotential and challenge
The current epidemiological focus on a
life course approach to chronic disease
emerged in the 1980s. However, the no-
tion that experiences in early life shape
adult health is not new. It was, in fact, a
prominent perspective in public health in
the first half of the century, but was
superseded by the life style model of
chronic disease which focused almost
exclusively on adulthood risk factors. This
was, largely, a result of the success ofcohort studies in confirming, for exam-
ple, smoking or high cholesterol levels as
major risk factors for several chronic dis-
eases.
The current revived emphasis on a life
course perspective has arisen against a
background of increasing evidence, espe-
cially from revitalised historical cohorts,
maturing birth or child-cohort studies,
that the risk of many NCDs such as CVDor diabetes is not just determined by risk
factors in mid-adult life, but already
begins in childhood or adolescenceand
potentially even earlier during fetal
development.Specifically, it has been boosted by
prominence given to (a) the increasing
evidence on the tracking
of conventional risk fac-
tors from childhood to
adulthood from large and
extended cohort studies
such as the Bogalusa
Heart Study (e.g. Bao et al.
1994); (b) the rise ofpro-gramming as a model of
disease aetiology, in par-
ticular the fetal origins of
adult disease hypothesis
(Barker, 2000); and (c)
emerging evidence to indicate that some
early risk factors may act across genera-
tions thus increasing cardiovascular risk
in offspring (Sterne et al. 2001; Davey
Smithet al.
2000a).Whilst consideration of early life fac-
tors or exposures is a main focus of the
life course perspective, it is much broader
than that. Its aim is to transcend the di-
chotomy between traditional adult life-
style and early origins models of adult
disease, both of which, on their own, are
unable to fully explain individual risk as
well as geographical, social and temporal
variations in disease patterns (Kuh and
Ben-Shlomo, 1998).
Thus, the life course perspective con-
siders the social and physical hazards, and
the resulting behavioural, biological and
psychosocial processes, that act across all
stages of the life spangestation, infancy,
childhood, adolescence, young adulthood
and midlifeto affect risk of disease later
on. It considers, in particular, the exist-
ence of both critical and sensitive
periods throughout life where exposuresare deterministic or especially powerful
WHO recognises the
potential of the life
course perspective to
enable policy-makers to
identify the most
effective and appropriate
prevention strategies andto gain maximum
leverage for interventions
where prevention
resources may be scarce.
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9
in predisposing to, or lessening risk of dis-
ease later on. The term critical period
implies exposures that must occur in
some specified window(s) of time andoften involve exposures that alter normal
biological development. Sensitive period
exposures refer to a broader class of in-
fluences that may have greater impact on
later outcomes if they occur in certain
periods than in others. In empirical terms,
both critical and sensitive period expo-
sures imply time by exposure inter-
actions. Better under-
standing of critical andsensitive period expo-
sures thus offers the
potential for identifying
the most appropriate
and effective interven-
tions or strategies for dis-
ease prevention or
health promotion. In
addition, a life course
perspective on NCDsinvokes concepts of
accumulation of both
correlated or uncorre-
lated exposures that over time additively
increase the risk of adverse outcomes.
The major challenge in harnessing the
potential of the life course perspective for
public health policy is to fully elucidate
the pathways and mechanisms by which,
in different populations and at different
historical periods, factors or exposures in
earlier and later life act to determine sub-
sequent risk of disease. Of particular im-
portance is to identify the relative role of,
and interaction between, earlier and later
factors, and the critical periods and expo-
sures that may shape chronic disease risk
later on.
So far, and on the basis of available
evidence, several theoretical models have
been advanced to explain the possibleways in which factors over the life course
may act to cause chronic disease (Ben-
Shlomo and Kuh, 1999).
1. A critical period modelwhere aninsult during a specific period of growth
or development has a lasting, life long
effect on physical functioning or struc-
ture thus resulting in disease later on.
2. A critical period with later effect
modifierswhere later factors may
modify such a risk earlier incurred.
3. Accumulation of riskwith independent and
uncorrelated results
where separate and inde-
pendent risk factors at
each stage of life combine
to raise disease risk.
4. Accumulation of risk
with correlated results
where risk factors clusterin socially or biologically
patterned ways, and may
raise the risk of disease
through social and/or biological chains
(or pathways) of risk. That is, where one
adverse (or protective) experience will
tend to lead to another adverse (or pro-
tective) experience in a cumulative way.
Disentangling the ways in which factors
at each stage of life act or interact to shape
disease risk is, obviously, complex and dif-
ficult. This is added to by the fact that
explanations are not only disease specific,
but may also vary from one cohort, popu-
lation, or context to another. It is crucial
to understand that the effects of early life
exposures on later disease risk are likely
to be highly contextualized in both time
and space. For example, being born into
poverty in Bangladesh in 2000 is likely tobe associated with very different early life
PART I. LIFE COURSE AS A CENTRAL PART OF WHOS WORK ON NCD PREVENTION AND HEALTH PROMOTION
The life course
perspective considers the
social and physical
hazards; and the resulting
behavioural, biological
and psychosocial
processes, that act across
all stages of the life
spangestation, infancy,
childhood, adolescence,
young adulthood and
midlifeto affect risk ofdisease later on.
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exposures than being born into poverty
in the USA in the 1950s. The social mean-
ing of poverty and its life course links to
particular types of exposures, as well as
the prevailing disease environment will
all influence the potential for early life
factors to be expressed in different ad-
verse outcomes later in life.
Despite the complexity and difficulty
of the challenge, and despite the fact that
work is only in its early stages, a critical
mass or body of evidence, in particular
from developed countries, has accumu-
lated over the last decade.
The time is thus now ripe for taking a
first step towards capturing some of the
potential of the life course perspective for
policyby taking stock of what knowl-
edge has accumulated, by considering
what policy implications are already
emerging, and by pinpointing the key
gaps in knowledge that need to be ad-
dressed by future research.
10
LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
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PART II
Key themes andgaps in current evidence
on life course linksto disease
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2.1 Introduction
Most of the relevant evidence comes
either from historical or retrospec-tive cohort studies, or from ongoing orrecently established prospective birth orchild cohort studies. A selection of someof the former studies, which are mostlyfrom developed countries, include:
UKthe 1946 and 1950 birth cohorts;the Hertfordshire, Sheffield, and Caer-philly cohorts (see Leon and Ben-Shlomo, 1997); the Glasgow University
Students cohort (McCarron et al. 1999);and the Boyd Orr cohort (Gunnell etal. 1998a)
USthe Harvard Alumni Studies(Paffenbarger and Williams, 1967) orJohns Hopkins Precursor Study (e.g.Klag et al. 1993)
Finlandthe Helsinki Central Hospi-tal Cohort (Eriksson et al. 1999)
Netherlandsthe Dutch Famine Co-hort (e.g. Ravelli et al. 2000)
Russiathe Leningrad Siege Cohort(Stanner et al. 1997).
Swedenthe Uppsala cohort (e.g.Leon et al. 1996, 1998)
A few such cohorts have, however, alsobeen studied in developing countries, forexample in Mysore, India (Stein et al.
1996; Fall et al. 1998) or Beijing, China(Mi et al. 2000).
Prospective child or adolescent cohortstudies, too, are predominantly fromdeveloped countries, e.g.
USthe Bogalusa Heart Study(Berenson et al. 1991)
UKthe ALSPAC Study (ALSPAC,2001)
Finlandthe Young Finns Study(kerblom et al. 1999).
However, several developing countrychild cohort studies do exist including:
India
the Pune Birth Cohort(Bavdekar et al. 1999) and the Pune Ma-ternal Nutrition Studies (Fall et al.1999)
South Africathe Birth to Ten Studyin South Africa (Yach et al. 1991).
A few retrospective child cohort stud-ies, such as for example in Jamaica(Forrester et al. 1996), the Gambia(Margetts et al. 1991), Zimbabwe (Woelket al. 1998), or the Democratic Republicof Congo (Longo-Mbenza et al. 1999),have provided further evidence on earlylife course risk factors in developingpopulations.
Additional developing world insightscome, moreover, from child health andnutrition surveys such as the CEBU Lon-gitudinal Health and Nutrition Survey inthe Philippines (CLHNS) (Cebu Study
Team, 1991) or the INCAP NutritionSupplementation Trial in Guatemala(Martorell, 1995). Whilst these studies didnot specifically set out to investigate lifecourse impacts on chronic disease risk,some of their findings are, nevertheless,relevant.
The experts assessment of thecurrently available evidencein theirwritten comments prior to, and their dis-
cussions at the meetinghas clearlyshown the complexity of trying to disen-tangle the various life course influencesthat act to shape the risk of CHD, strokeand diabetes. They have highlighted, inparticular, the limitations imposed by theserious lack of evidence from developingcountries.
Despite the complexity and limita-tions, however, the assessment has alsoshown that much knowledge has already
accumulated and that it is possible toidentify key themes in evidence, key
PART II. KEY THEMES AND GAPS IN CURRENT EVIDENCE ON LIFE COURSE LINKS TO DISEASE
13
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
emerging implications for policy, and pri-
ority areas for future research. These are
presented in the subsequent sections.
2.2 Key themes and gaps inevidence on life course
links to disease
The following key themes and factors are
identified as characterizing the influence
of life course factors on risk of CHD,
stroke and diabetes in different popu-
lations. At the same time, the main gaps
in knowledge are highlighted.
2.2.1 Key general points
Three general, but extremely important
issues regarding the use of the life course
perspective for policy, warrant re- empha-
sis at the outset:
a. Risk of disease isinfluenced by factorsat all stages of thelife course
The risk of developing
CHD, stroke or diabetes
is influenced by biologi-
cal or social factors act-
ing at all stages of the
life coursein fetal life,
childhood, adolescence,
and adulthood.
Life time risk, how-ever, cannot simply be
understood as an addi-
tive model: Earlier and later factors are
likely to interact, and the consequences
of some influences may depend on events
at earlier (or later) critical stages of de-
velopment. For example, negative conse-
quences of fetal growth retardation
appear especially in conjunction with
high post-natal weight gains. The relativeimportance of early and later factors in
causing later disease, however, is not yet
fully understood.
b. Life course influences aredisease specific
CHD, stroke and diabetes are likely not
the results of the same processes and
exposures acting over the life course. The
life course influences on risk are specific
for each disease, or even subtype of
diseaseas, for example, for haemor-
rhagic and ischaemic strokethus posing
important challenges for research and for
integrated policy development.
c. Life course impacts on disease arepopulation (and cohort) specific
Life course impacts on disease cannot
simply be generalized from one popula-
tion to the next, or from one cohort to
the next. Important differences appear to
exist, reflecting either genetic differences
and/or differing social,
economic, cultural and nu-tritional contexts, and dif-
ferences in the manner of
gene expression across a
variety of environmental
conditions. What deter-
mines population or
cohort differences, par-
ticularly what the relative
role is of different social
contexts, is not well under-
stood, but is a key area for
future research.
2.2.2 Disease and established
risk factors over the life
course
a. Known risk factors remainthe most firmly establishedlink to disease
The risk behaviours of unhealthy diet,lack of exercise, and tobacco use, and the
The risk behaviours of
unhealthy diet, lack of
exercise, and tobacco use,
and the associated
biological risk factors of
high blood pressure,
obesity and dyslipi-
daemia, remain the most
firmly established risk
factors for CHD, stroke
and diabetes.
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15
associated biological risk factors of high
blood pressure, obesity and dysl ipi-
daemia, remain the most firmly estab-
lished risk factors for CHD, stroke anddiabetes.
Efforts to disentangle the life course
impacts on- and effects of these risk fac-
tors, especially in developing countries,
are seriously hampered by the dearth of,
and methodological limitations in the ex-
isting studies on their prevalence, social
patterning, and trends. The latter include
the inability of body mass index (BMI),
as the most commonly used index of obes-ity, to adequately distin-
guish between lean and
fat tissue; the methodo-
logical di fficu lties of
accurately identifying hy-
pertension; and the lack
of appropriate population
norms for both blood pres-
sure and adiposity.
Nevertheless, severalkey issues can be identi-
fied.
b. Rising risk factor trends:obesity and tobacco use
The little evidence that exists shows that
in the developing world, the prevalence
of the major risk factors obesity and
tobacco use is rising.
In developed and developing
populations the prevalence of obesity
among both adults and children has
shown sharp increases, somewhat off-
setting the progress made with some of
the other biological risk factors in many
countries. The rise in obesity particularly,
is a reflection of the increased marketing
and availability of a westernised diet rich
in refined foods, saturated fats, sugar and
salt (the nutrition transition), as well as
changes in lifestyles towards decreasedphysical activity.
Tobacco use, though declining in some,
mainly developed country populations, is
showing alarming rates or increases in
others. A particularly worrying trend isthe marked rise in smoking amongst
women and teenagers in many develop-
ing and developed countries.
c. Major biological risk factorsemerge and act in early life
Contrary to what was long assumed, high
blood pressure, dyslipidaemia, impaired
glucose tolerance (IGT), and obesityalready emerge in child-
hood and adolescence,
and are often clustered
together. Obesity, espe-
cially abdominal adipos-
ity, seems to play a
central role in the devel-
opment of the other fac-
tors, although some race
and gender differences inthe clustering of risk fac-
tors do appear to exist.
Three critical periods
or exposures in early life appear to in-
crease the risk of developing obesity that
persists into adulthood: 1) exposure to
gestational maternal diabetes and high
birth weight; 2) an early adiposity re-
bound (the age at which BMI increases
after its nadir in early childhood), and 3)
development of obesity in adolescence.
The mechanisms underpinning these
apparent associations are not yet under-
stood.
The presence of risk factors early in
life already influences risk of later dis-
ease, either through the social and bio-
logical tracking of these behaviours over
time, and /or through their direct biologi-
cal effects. Obesity, high blood pressure
and dyslipidaemia track from childhoodthrough to adolescence and young adult-
PART II. KEY THEMES AND GAPS IN CURRENT EVIDENCE ON LIFE COURSE LINKS TO DISEASE
Contrary to what was
long assumed, high blood
pressure, dyslipidaemia,
impaired glucose
tolerance (IGT) and
obesity already emerge in
childhood and
adolescence, and often
clustered together.
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
hood, where they lead to atherosclerosis
and, in many cases, diabetes. The pres-
ence of risk factors in adolescence or
young adulthood (e.g. high blood pres-sure) has additionally been shown to in-
dependently predict an increased risk of
CVD later on.
The relative predictive power of risk
factors present in childhood, compared to
risk factors in mid-life will depend on the
disease concerned. In many cases, how-
ever, it is indicated to be equal, if not
stronger, than that of risk factor presence
in mid-adulthood.What is not yet understood, for exam-
ple in the case of blood pressure, is the
relative importance of long-term expo-
sures to raised levels as opposed to acute
high transient levels. In
the case of obesity and
insulin resistance syn-
drome it appears that
long -term exposure to
obesity has an aggravat-ing effect. Risk factors in
early life, particularly
tobacco use and obesity,
moreover, not only affect
ones own later health but
also the health of the next generation.
Obesity, especially in mothers, for
example, clearly increases the risk of
obesity and, consequently, disease risk in
their offspring.
Similarly, tobacco use during preg-
nancy is strongly linked to low birth
weight and associated disease or mortal-
ity risk in the offspring. Parental
smoking, moreover, exposes children to
environmental tobacco smoke (ETS), and
thus an increased risk of asthma, certain
infections and reduced lung functioning.
2.2.3 Disease and unhealthy
lifestyles over the life
course
a. Unhealthy lifestyles drivethe emergence of disease risk inearly life
Unhealthy lifestylestobacco use, physi-
cal inactivity and unhealthy diet (a diet
high in sugar, saturated fat, salt and
calorie content)are already taken up by
children, leading to the early develop-
ment of obesity, high blood pressure,
dyslipidaemia, IGT and the associated
disease risk. In addition, unhealthy life-
styles in early life, for example physical
inactivity, are shown to independently
predict later CVDregardless of their
presence in mid or late adulthood.
Unhealthy lifestyles
are taken up by children
or adolescents largely as
a result of massive mar-
keting and media pres-
sures, as well as parentsown health behaviours.
Parents lifestyles, for ex-
ample, have an important
impact on children s
dietary habits, level of physical activity,
and uptake of tobacco use.
b. Socioeconomic position over thelife course influences risk factordevelopment
The prevalence of behavioural or biologi-
cal risk factors is clearly influenced by
socio-economic position (SEP) over the
life course. In adults, for example, the
prevalence of risk factors is not just de-
termined by adult SEP, but also by their
socioeconomic position in childhood and
the different social trajectories that indi-
viduals traverse as they become educated,
enter the labour market, generate in-
come, change jobs, and gather assets.
In developed countries, prevalence of
The prevalence of
behavioural or biological
risk factors is clearly
influenced by socio-economic position over
the life course.
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17
risk behaviours and factors among adults,
just as prevalence of disease, is generally
higher among those from lower socio-eco-
nomic strata. Similarly, it is typicallypoorer childhood SEP that is associated
with more risk behaviour, suggesting that
early socio-economic disadvantage may
increase later disease risk through devel-
opmental processes whereby children
adopt particular detrimental behaviours
and attitudes.
Poor early SEP can also
have inter-generational
effects on disease risk.Among young females in
Japan, for example, rais-
ing SEP through education
has been shown to not
only decrease their own
risk of disease, but also
that of their offspring in
the next generation.
(Hasegawa, personal communication)
The general developed country patternof low SEP=high risk, however, clearly
does not hold in all cases. The effect, det-
rimental or protective, of SEP on risk
behaviours can differ considerably be-
tween populations, ethnic groups, cohorts
and genders. For example, among older
women cohorts, low early SEP was shown
to protect against smoking, whereas
among younger cohorts at present it is
associated with an increased risk.
In developing countries the social gra-
dient of disease risk is commonly
assumed, and often found to be opposite
to that in developed countries. Risk fac-
tors are often highest in those population
groups that are the most westernised or
moderni.e. the affluent, urban popula-
tion. However, the patterns of risk are at
times more complex and do not follow
this uniform pattern. Obesity, for exam-
ple, is emerging as a serious problemamong the poor in Latin America. In
India, smoking rates are found to be
higher in rural than in urban areas.
c. Importance of the macro-structural context
The specific socio-economic and rural-
urban risk factor patterns that prevail in
different populations are shaped, to a
large degree, by the underlying macro-
structural contextthe prevailing social,
economic, political and cultural forces.
These forces determine
the exposure to risk in-
ducing environments,the resources necessary
and available to opt for
healthy lifestyles, and
the social meaning that
risk behaviours have for
different population
groups.
For the developing
world in particular, this means that the
processes by whichurbanisation
and
de-
velopment lead to increased risk cannot
simply be assumed to be the same across
different societies.
d. Additional influence ofpoor childhood SEP
The relationship of poor early SEP to risk
factors or behaviours only partly explains
its association to later disease. The clear
link of lower early SEP to CHD and stroke,
which is reflected in the consistent asso-
ciation shown between short stature (i.e.
impaired linear growth) and these dis-
eases is possibly mediated by two other
factors.
Infectious factors
A first factor thought to possibly under-
pin the association of poor childhood SEP
to CVD is early exposure to infectious
agents. The specific bacterial pathogens
PART II. KEY THEMES AND GAPS IN CURRENT EVIDENCE ON LIFE COURSE LINKS TO DISEASE
The processes by
which urbanisation and
development lead to
increased risk cannot
simply be assumed to be
the same across different
societies.
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
that appear linked to poor conditions and
have so far been implicated include
Helicobacter pylori and Chlamidia
pneumoniae, though evidence is far fromconclusive.
A further, possibly infectious but yet
unidentified factor is assumed to under-
pin the particularly consistent association
that is seen between poor childhood SEP
and haemorrhagic stroke.
The possible role of other infectious
agents in the development of chronic dis-
ease risk, especially in developing coun-
tries where infectious disease is stillpervasive, has not yet been explored.
Nutritional factors
A further indirect way in which childhood
deprivation, especially nutritional depri-
vation, may be associated to a raised dis-
ease risk, is through the apparent
association between stunting (especially
severe stunting) and an increased risk of
(abdominal) adiposity.This association is possibly
due to impaired fat oxida-
tion in stunted children
and a consequent in-
creased susceptibility (in
terms of weight gain) to
high fat urban diets.
A link between stunting
and risk of central adipos-
ity would be of particular importance inthose developing countries who have re-
cently or are currently undergoing the
nutrition transition.
2.2.4 Disease risk and protective
factors in childhood
a. Breastfeeding
In contrast to the detrimental effects of
unhealthy diet and lack of exercise in
childhood, breast-feeding is indicated to
have a protective effect on the develop-
ment of disease risk.
Apart from its well-established short
term benefits for child health and devel-opment, breast-feeding is increasingly
indicated to confer a lower risk of high
blood pressure, as well as of dyslipidaemia
and obesity. However, this protective
effect is not yet unequivocally estab-
lished, as some weak evidence of a long-
term negative impact of breastfeeding on
CVD risk exists.
2.2.5 Disease, risk factors and
fetal growth
In addition to factors in childhood and
adolescence, factors relating to fetal
growth are clearly involved in shaping
risk of disease.
a. Fetal growth and later disease
In many populations intrauterine growth
retardation (IUGR) (as in-dexed by small size at
birth or exposure to fam-
ine in gestation) is shown
to be associated with a
higher risk of CHD,
stroke and diabetes. This
association forms the ba-
sis of the Barker or the
Fetal Origins of Adult
Disease (FOAD) hypothesis. Some evi-
dence suggests moreover that this risk
may be transmitted intergenerationally.
At the same time, however, large size
at birth, too, is found to be linked to an
increased risk of diabetes or CVD. Thus,
the relationship of fetal growth to later
disease is, in fact, U-shaped. This effect
of fetal overnutrition is important to bear
in mind, particularly in view of the cur-
rent prominence of the FOAD hypothesis
In addition to factors
in childhood and
adolescence, factors
relating to fetal growth
are clearly involved in
shaping risk of disease.
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19
b. Fetal growth, blood pressure,dyslipidaemias and impairedglucose tolerance (IGT)
In addition to its link to adult disease,IUGR is clearly found, in both adults and
children, to be associated to a higher risk
of high blood pressure and impaired glu-
cose tolerance. Its association to the most
important dyslipidaemias (i.e. high trig-
lyceride and low HDL-c levels) is less
clear cut.
At least in a statistical sense, the asso-
ciation of IUGR to these biological risk
factors does not appear to mediate its linkto CVD, though this may reflect the limi-
tations of available data. In the case of
diabetes, a mediating effect of the asso-
ciation to IGT seems more indicated.
c. Population and cohortdifferences: importance of thepost-natal context
Though associations between IUGR and
disease risk are found in most populations
studied, some evidence shows conflicting
results, indicating the existence of impor-
tant population and cohort differences in
the relationship of fetal growth to later
disease. Examples include the apparent
lack of an association between small size
at birth and diabetes in Indians; the ab-
sence of a relationship between IUGR and
blood pressure in some black populations;
and the divergent relationship between
IUGR and impaired glucose tolerance inchildren and adults in India.
These population and cohort differ-
ences may reflect underlying genetic dif-
ferences, expression of genes, and/or the
impact of divergent post-natal contexts
and environments. The latter may reflect
differences in a particular populations
stage of the epidemiological or nutritional
transition or, between cohorts of the same
population, the result of rapid social andeconomic change.
d. Interaction between IUGR andlater weight or height gained:importance of post-natal nutrition
Increasing evidence indicates the associa-tion between IUGR and later disease risk
is somehow mediated or enhanced by the
rate of growth in weight or height in child-
hood or adolescence.
The apparent role of growth in weight
or height is indicated by three factors:
in most cases significant associa-
tions between low size at birth and
later disease risk factor are only
found afteradjustment for currentweight
in many cases the association be-
tween low birth weight and disease
risk is strongest in those with high-
est BMI or fatness
in some studies the association
between IUGR and disease risk is
shown to be highest in individuals
who have had accelerated growthin height to become tall.
It is not yet clear how this apparent
effect of post-natally gained weight or
height is to be interpreted, but four (not
mutually exclusive) interpretations are
possible:
i. It represents a negative effect of
enhanced growth in childhood or ado-
lescenceper se. In other words, accel-
erated growth in weight (or height)
itself could have negative conse-
quences.
ii. It is the difference in size between birth
and the later stage that better defines
detrimental impaired early growth: the
higher the difference, the higher the
risk (see e.g. Lucas et al. 1999).
iii.Obesity reveals/activates an underly-
ing susceptibility induced by impairedearly growth and, vice versa, low birth
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
weight enhances the risk associated to
obesity, i.e. obesity is particularly
harmful in those with early growth re-
tardation.
iv. The effect of enhanced growth in
height in IUGR babies may reflect a
failure of the fetus to realise its genetic
growth potential in utero, possibly due
to placental failure. It may be this in-
sult on fetal growth that underlies the
increased risk of disease (e.g. Leon et
al. 1996).
Whilst the particular interpretationmay depend on the specific disease or risk
factor concerned, they all indicate the
importance of an adequate post-natal
nutritional environment in bringing to
the fore a risk associated with fetal growth
retardation.
Further evidence for this comes from
the discrepant findings of the two exist-
ing famine studies. Whereas an associa-
tions between exposure to famine and
later disease risk were found in the Dutch
famine, which was fol-
lowed by a period of ad-
equate nutritional supply,
no association was found
in the Russian famine,
which was followed by a
long period of inadequate
nutritional supply. An-
other indication of the im-
portance of the post-natalnutritional context are the
marked rural-urban dif-
ferences in CVD and diabetes risk, for ex-
ample in India. While low birth weight is
more common in rural areas, disease risk
is much higher in the nutritionally more
adequate urban areas (e.g. Yajnik, 2000).
e. IUGR and increased risk of
obesitya paradox?The crucial question of whether IUGR
also enhances the risk of obesity in a nu-
tritionally rich post-natal environment
(i.e. the thrifty phenotype hypothesis) is
still unresolved.The available evidence is inconclusive
and presents a paradox by consistently
showing a positive, often linear, relation-
ship between birth weight and obesity
(BMI) which is difficult to reconcile with
the association between low birth weight
and higher risk of disease.
A possible explanation of this paradox
may lie in the inadequacy of BMI to ad-
equately measure fatness, thus disguisinga possibly important relationship between
low birth weight and greater risk espe-
cially of central body fat.
f. Mechanisms underpinningthe association of fetal growthto disease risk
The mechanisms and processes under-
pinning the association between retarded
fetal growth and later disease risk remainpoorly understood.
The generation of a
greater understanding
has, amongst others, been
hampered by the some-
what haphazard use of
multiple measures of
birth size, and by the limi-
tations of low birth weight
(the currently most com-
monly used index of fetal
growth retardation) as an
adequate marker to capture the range of
possibly important exposures or birth
outcomes.
The main unresolved issues include
the following:
the relative role of environmental
versus genetic exposures
the nature and role of inter-generational transmission of risk,
The mechanisms and
processes underpinning
the association between
retarded fetal growth
and later disease risk
remain poorly
understood.
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21
including the role of maternal ges-
tational diabetes, and parental body
size and nutritional history
the nature of the exposures that may
lead to detrimental fetal growth
retardation in par-
ticular the role of
maternal nutrition
in this
the potential impor-
tance of the timing
of insults in utero
the potential endo-
crine, metabolic and
haemodynamic ad-
aptations that may
occur in the fetus in
response to insults,
in particular the population rel-
evance of the apparently important
adaptations in the cortisol stress re-
sponse system.
the nature and significance of the
apparent mediating effect of rapid
post-natal weight and height gain, in-
cluding the questions as to why
catch-up growth is detrimental? and
whether it has to occur in a specific
period to be detrimental?
2.2.6 Importance of fetal
vs. post-natal factors forpopulation trends in
disease
a. A greater importance ofpost-natal factors
The clear association of both fetal and of
post-natal factors (incl. the classical es-
tablished risk factors) to risk of CHD,
stroke and diabetes raises the crucial
question as to the relative importance of
fetal vs. later factors in determining popu-
lation patterns and trends in disease.
The evidence so far points to a limited
role of fetal factors. Serious doubts exist
concerning the causality of their associa-
tion to disease, and indications are thattheir population attributable risk is small.
The rapid increases as well as the social
patterns of risk factors,
CVD, and diabetes in de-
veloping countries, are
clearly not explained by
changes in fetal growth.
Impaired fetal growth
(low birth weight) has
been pervasive for along time whereas the
epidemic in CVD and
diabetes are a recent oc-
currence. In most coun-
tries, moreover, disease
rates are much higher in urban areas al-
though birth weights are much lower in
rural areas.
The temporal trends and patterns of
risk factors and disease in populationsthus seem largely related to changes in
post-natal lifestyle and environment. The
period in which the trends, for example
of CVD in developing countries, have
evolved is too short for any changes in
the gene pool to account for them.
b. Interaction (potentiating effect)between fetal and post-natal effects
Despite questions over the limited direct
role of fetal factors in determining trends
and patterns of disease, they may never-
theless have a potentially important in-
fluence if their effects depend in part on
interactions with exposures in later life.
The association of IUGR to risk factor
development as well as its apparent in-
teraction with obesity to enhance risk of
disease suggests that, in many popu-
lations, fetal undernutrition may increase
susceptibility to the adverse effects of lifestyle or environmental change. In addi-
PART II. KEY THEMES AND GAPS IN CURRENT EVIDENCE ON LIFE COURSE LINKS TO DISEASE
In many populations,
fetal undernutrition may
increase susceptibility to
the adverse effects of life
style or environmental
change. In addition, it
may have a potentiating
effect on the risk of
disease associated with
obesity.
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tion, it may have a potentiatingeffect on
the risk of disease associated with obes-
ity. These effects, given the apparent
intergenera-tional transmission of risk as-
sociated to fetal growth, may last not just
for one, but for several generations.
A potentiating effect of fetal growth re-
tardation (which in statistical analyses
would manifest in steeper slopes in the
link between obesity and disease found
in developing compared to developed
countries) would have grave implications
for the expected future rates of disease in
the developing world.
22
LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
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PART III
Emerging policyimplications and research
priorities
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3.1 Emerging implications
and recommendations
for policy
In light of their assessment of the stateof the art evidence regarding life courselinks to the risk of CHD, stroke, and dia-
betes, several implications for policy have
been identified by the experts, and a set of
firm recommendations have been made.
3.1.1 The challenge for
integrated policy
Whilst carrying a great potential for dis-
ease prevention, the move from research
to policy based on the life course impacts
on disease presents a great challenge. The
disease specific nature
of life course impacts
on disease risk means
that integration of
policies may be diffi-
cult. There are no
simple models such as,for example, in the case
of tobacco.
Policies specifically
geared to reducing the
risk of one disease, may
have no, or even ad-
verse effects on the risk of another. Poli-
cies may, moreover, have different effects
in different settings and cohorts, and
could have possible unintended detrimen-tal outcomes in the short term.
Much more, therefore, needs to be
known about the life course influences
on various diseases, in particular what
aspects may be common to them, what
trade-offs exist between short and possi-
ble long-term outcomes, and what effects
prevail in different environmental con-
texts and in different cohorts. This not-
withstanding, some clear implications
and recommendations for policy already
emerge.
Given that the scientific knowledge on
life course and disease is still evolving,
these recommendations are placed in a
hierarchy according to the firmness of
currently available evidence.
1. Firm positive recommendationsfor policy
Continue focus on major knownrisk factors
The major known risk behaviours
unhealthy diet, physical inactivity and
tobacco useand the associated biologi-
cal risk factors of obesity, high blood
pressure, dyslipidaemias, remain the
most firmly established causal factors for
CHD, stroke and diabetes. These factors
should therefore remain
the focus of prevention
policy.
Fetal factors, given
their potential impor-
tance in shaping risk of
disease, also need to beconsidered. Above all,
efforts are needed to de-
velop a fuller under-
standing of the nature
and basis of their effect.
Prevention policies
should specificallyfocus on tobacco use
and obesity.
Prevention of tobacco use and, perhaps
more importantly, reductions in total ex-
posure to smoking over the life course by
encouraging young adults to stop, must
be a priority given its clear and revers-
ible link to CVD and certain cancers; its
alarming and rising prevalence among
women and youth in many countries; and
its detrimental effect not only on the
health of those who use tobacco but also
of the next generation.
A focus on obes ity prevention is
needed in view of the alarming global
rises in its prevalence; its central role in
PART III. EMERGING POLICY IMPLICATIONS AND RESEARCH PRIORITIES
The major known risk
behavioursunhealthy diet,
physical inactivity and
tobacco useand the
associated biological riskfactors of obesity, high blood
pressure, dyslipidaemias
should remain the focus of
prevention policy.
25
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
the development of other risk factors; its
potential interaction with retarded early
growth to enhance disease risk; and fi-
nally its adverse effect also on the healthof the subsequent generation.
In developing countries, obesity pre-
vention policies must go hand in hand
with strategies to prevent undernutrition.
Need for strategies of primary andprimordial prevention
Given that risk behaviours and factors are
more commonly established in childhood
and adolescence and track through toadulthood, and given the difficulty of re-
versing especially obesity in adulthood,
strategies of primary and primordial pre-
vention are of utmost importance
though high risk lifestyle intervention
strategies can clearly also be effective.
Primary prevention strategies should
be aimed particularly at children, and
preferably involve school-
based heal th educationand promotion pro-
grammes, focusing on
behavioural and psycho-
social components and
aimed at promoting
healthy diets, exercise and
reduced tobacco use. Such strategies must
be appropriate and responsive to the
particular setting and to the prevailing
cultural perceptions, for example regard-
ing body weight.
Targetingprimary prevention policies
at the following groups may be beneficial:
Young girls or women. Preventing
tobacco use will not just reduce their
own risk of disease but also the risk
of low birth weight and later disease
risk in their offspring. In the same
vein, preventing obesity in girls or
young women will not just benefit
their own health, but also the risk
of obesity and associated disease in
their children. Given the critical ef-
fect of obesity development in ado-
lescence, policies may perhaps focus
particularly on pre-puberty girls
Those socially or biologically disad-
vantaged from early life, for exam-
ple, those with low birth weight,
stunting, or exposed to gestational
maternal diabetes, or with parents
who are obese
Youth at those ages where particu-
lar lifestyles are adopted, i.e. where
programming of lifestyle occurs
Adolescents and young adults who
already smoke should be specifically
targeted by efforts to help them quit
smokingthe earlier one quits the
greater the benefit
Primary prevention strategies must be
underpinned and complemented by
policies of primordial
prevention. Such policies
must address the various
macro-structural social,
economic, and cultural
forces that influence and
determine (or protect
from) the uptake of risk
behaviours among differ-
ent populations in different settings, in
particular in the developing world.
Specifically, such policies should aim at:
Reduction of advertising or positive
cultural representations of known
risk factorse.g. tobacco or un-
healthy foods
Wide use of smoke-free environ-
ments
Fiscal policies to reduce smoking
Promotion of public healthy food
policies
Reduction of the influence of big
Strategies of
primary and primordial
prevention are of
utmost importance.
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27
food corporations, especially on the
young
Encouragement of public and pri-vate partnerships. This is the most
realistic and promising way to move
forward on creating healthy devel-
opmental environments, in particu-
lar with regard to adoption of risk
behaviours such as tobacco use, poor
diet and lack of physical activity.
Reduction of poverty
Reducing poverty and increasing educa-tion will improve childrens health trajec-
tories both in relation to infectious and
non-communicable diseases. Among
girls, such strategies will not just improve
their own health trajectories, but also that
of their offspring in the next generation.
Policies, specifically to prevent severe
undernutrition and stuntingas have
already been successfully pursued in
some populationsare likely to increase
work capacity, intellectual functioning
and educational achievement, and reduce
risk of developing central adiposity. By
additionally lowering the risk of low birth
weight in offspring, such interventions
may also reduce disease risk in the next
generation. Concrete interventions, thus,
could thus take the form of public sup-
port for nutrition programmes from in-
fancy through school.
2. Unspecified recommendations
No clear direction regardingfetal growth
Despite the high profile of evidence link-
ing early life factors such as impaired
fetal or childhood growth to risk of later
disease, no firm policy recommendations
can yet be made.
First, there are potentially important
short and long-term negative effects andtrade-offs of strategies to increase fetal
growth. For increased fetal growth these
include, in the short term, a raised risk
for obstetric complications through grow-
ing larger babies in many developingpopulations. In the long term they may
cause a possibly increased risk of other
chronic diseases: higher birth weight and
stature, for example, are associated with
a higher risk of some neoplasms.
Second, the U-shaped relationship
between size at birth and risk of later dia-
betes or CVD, as well as the existence of
apparent population and cohort differ-
ences in the association between fetalgrowth and later disease, indicate that no
clear direction can yet be given in terms
of what is the optimum birth size to
target for.
Third, current evidence casts serious
doubt on the feasibility and effectiveness
of currently available interventions to
modify fetal growth, in particular through
maternal nutrition. Some strategies such
as protein supplementation of maternaldiet have, moreover, been shown to have
negative effects including increased fetal
mortality and reduced birth weight.
No direction on initiation, duration andexclusivity of breastfeeding
Though breastfeeding seems promising as
a protective factors against CVD and dia-
betes risk, the existence of evidence sug-
gesting also potentially adverse long term
consequences means that no specific rec-
ommendations can yet be made regard-
ing initiation, duration and exclusivity.
However, given its indisputable benefits
to overall childhood mortality, unquali-
fied support is given to breastfeeding
per se.
Reducing stress
There is some, though weak, evidence to
suggest that general strategies to reduce
stress in the adult environment (e.g. in
PART III. EMERGING POLICY IMPLICATIONS AND RESEARCH PRIORITIES
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
the workplace) may be beneficial in
reducing CVD riskperhaps especially in
poor populations, exposed to undernutri-
tion in utero.
3. Firm negative recommendationsfor policy
Do not discourage post-natal growth
Despite the existence of evidence show-
ing that under certain conditions, en-
hanced growth (in weight or height) in
childhood may be linked to a higher risk
of insulin resistance or cardiovascular
disease, this long term effect is out-
weighed by a far greater and more
certain and scientifically established ben-
efit in the short term for child health,
through its links for instance with greater
resilience to infectious diseases. Moreo-
ver, it is not yet clear in what particular
period in childhood rapid growth has a
detrimental effect. Strategies to reduce
such growth are therefore, at this point,
clearly not recommended.
3.2 Key priority areas forfuture research
The many gaps remaining in our knowl-
edge of how early and later factors
impact on risk of CHD, stroke and diabe-
tes, highlight the vital need for more re-
search. Only further research will be able
to provide the information base necessaryfor effective and appropriate policy de-
velopment in different populations.
The following four key areas have been
identified by the experts as priority
topics for future research:
1. Research on causes and interac-
tions
2. Trends analysis and surveillance
3. Intervention research
4. Refinement of methodology
1. Research on causes andinteractions
The core focus of, and challenge for
future research must be efforts to inves-tigate the early and later causes and
interactions of life course links to later
disease. Such research must address the
following questions:
a. The nature of the effects of fetal and post-
natal growth on later disease risk. This
includes the interaction between
intrauterine growth retardation and
rapid post-natal catch-up growth, and
obesity
b. The influence of maternal factors on
fetal growth and offsprings risk of dis-
ease. This includes maternal nutrition,
GDM, maternal cardiovascular func-
tion and maternal psychosocial factors
c. The biological mechanisms underlying
the association of fetal growth to later
disease risk. This includes the role of
stress and hormonal response systems,and intergenerational processes of risk
transmission
d. The association of infectious disease to
chronic disease risk. This includes the
possibly infectious factor underpin-
ning the particularly strong link of
poor child SEP to haemorrhagic stroke
e. The social, psychological, economic and
biological processes leading to unhealthy
lifestyles and risk factors in different
populations
f. The relative importance of early vs. later
life exposures on risk of disease at indi-
vidual and population level
g. The major risk factors for CVD and dia-
betes in developing country populations
Ideally, such research would involve:
Well designed prospective maternaland birth (or child) cohort stud-
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29
ies, to generate integrated life time
measures of growth, risk factors, socio-
economic, and psychosocial param-
eters. One opportunity in this respectwould be extension of the WHO road
to health studies of child health and
growth studies, beyond the age of five.
Historical cohort studies with avail-
able data sets on early growth para-
meters. Possible examples include the
Bambui or Pelotas longitudinal study
cohorts in Brazil, or possibly a cohort
from the 1956 famine in India. Poten-
tially valuable cohorts may also be
identified from past monitoring stud-
ies on maternal and/or child growth
and development, especially in devel-
oping countries. Efforts are necessary,
in this respect, to preserve and make
such existing data sets accessible.
Multi-generational studies, espe-
cially of migrants (and those remain-
ing in the country of origin). The by
now three generations of Asian
migrants in the U.K., as well as Japa-
nese migrants in Brazil may provide
important opportunities for this.
2. Trends analysis and surveillance
Investigations of causes and interactions
of life course links to later disease must
be complemented by research to estab-
lish and analyse trends in risk factors anddisease This would specifically involve:
a. Surveillance of trends and socio-economic
patterns in major risk factors
b. Surveillance of trends and patterns in
maternal and child health, nutrition and
growth
3. Intervention research
Investigations of causes and interactions,
and surveillance and analysis of trends
PART III. EMERGING POLICY IMPLICATIONS AND RESEARCH PRIORITIES
must be complemented by research to
asess the potential effectiveness and im-
pact of interventions. This specifically
includes:
a. Comprehensive policy reviews on actions
targeting under- and over-nutrition in
developing countries
b. Investigation of the efficacy, long and
short term effects (on both mother and
child) of interventions to increase birth
weight
c. Investigation of the short and long-term
outcomes of enhanced early growth for
infants born small
d. Establishment of the long term effects of
breastfeeding with regard to non commu-
nicable diseases
e. Research to identify ways of applying
current knowledge to prevention pro-
grammes
4. Methodological issues
Finally, for life course research to be as
effective as possible, efforts are necessary
to improve on existing, or foster certain
methodologies. This involves:
a. Improvement of measures of intra-uter-
ine growth retardation (alternatives to low
birth weight). These must reflect new
born body composition and fetal expo-
sures that may not necessarily beexpressed in birth size.
b. Improvement of measures of early socio-
economic disadvantage and psychosocial
experiences
c. Improvement of measures for adiposity,
and establishment of appropriate popu-
lation norms across the life course
d. Improvement of reliability and accuracy
of measures for blood pressure and es-
tablishment of appropriate population
norms
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LIFE COURSE PERSPECTIVES ON CORONARY HEART DISEASE, STROKE AND DIABETES
and diabetes present a vital starting point
for harnessing the potential of the life
course perspective to identify the most
appropriate and effective prevention poli-cies in different populations.
WHO, together with the group of ex-
perts who are committed to guiding and
supporting its efforts, is taking steps to
foster this life course initiative, through
collaborative work and consultation
across departments within WHO and with
partner institutions.
A specific focus of this work will be
the development, in consultation with theexperts, of a protocol for a multi-centre
comparative study to address some of the
key gaps in knowledge on life course and
NCD risk in different populations
especially in developing countries.
e. Development of specific measures for
underlying pathophysiological factors,
e.g. endothelial dysfunction
f. Conduct of comparative research between
populations at different stages of the epi-
demiological/nutritional transition, as
well as between cohorts. Comparative
analyses can powerfully illuminate the
role of the postnatal environment in
shaping disease risk in interaction with
early growth experiences.
3.3 Conclusion: Taking policyand research agendas
forward
The experts recommendations on policy
and research in light of current evidence
on the life course links to CHD, stroke
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